Compliance and Consistency with FDA Required Labeling

2016 was a year of interesting discussion around pharmaceutical manufacturers’ ability to communicate truthful and non-misleading, off-label information. The FDA settlement with Amarin over First Amendment litigation and the Agency’s two-day public hearing on manufacturer communications about unapproved uses of approved/clear medical products had those in the pharmaceutical industry and its support services hinged on FDA to see if, at last, it might provide further insight or guidance into how it currently views this complicated topic.

FDA has rung in the New Year aiming to set the record straight. On January 18^th, the Agency issued Procedural Guidance in Q&A format to help manufacturers understand FDA’s current thought process in evaluating manufacturer medical product communications to ensure consistency with the FDA-required labeling. In this Q&A, FDA makes it clear that consistency with the label is key and manufacturers must tell the truth. 

In addition to providing a list of three factors manufacturers should use to determine if product communications are consistent with the FDA-required labeling, FDA clarifies what is meant by information consistent with the FDA-required labeling. Information that is consistent with FDA-required labeling is limited to information about the approved or cleared uses of a product. At a minimum, the communication must be in-line with certain condition for use information found in the FDA label. Specifically, the communication must be for the same indication, represent the same patient population, adhere to the limitations and directions for use and dosing and administration information as outlined in the product’s FDA-required label. These particulars present just one group of factors that FDA considers in its consistency evaluation. 

The remaining two factors further reinforce FDA as a protector of public health. If the communication alters the risk-benefit profile of a product in a way that increases potential for harm to health, or if the communication suggests or implies the product could be used in a way that is inconsistent with the directions for use in the FDA-required labeling, then the communication would not be consistent with FDA-required labeling. 

Though FDA recommends that manufacturers use this set of three factors to evaluate whether communications are consistent with the FDA-required labeling, the Q&A also reinforces standards of truthfulness. While consistency with the label is critical to ensure the communication of any information not contained in the FDA label does not misbrand the drug, accurate context around this information (e.g. revealing material facts, disclosing appropriate support of facts and science, accurate characterization of evidence) is an absolute must to help ensure the communication does not misbrand the drug. Of note, FDA does warn manufacturers that should they rely on inadequate studies to support their communications, simply disclosing the material limitations of the study does not correct the misleading message. In other words, if the study design is not sufficient, simply disclosing the type of study with its constraints does not justify communicating the message. FDA states while it “…would not consider….a communication that is consistent with the FDA-required labeling to be false or misleading only on the lack of evidence sufficient to satisfy the applicable approval/clearance standard” it is clear that such a communication “…could be false or misleading for other reasons.” Examples in the Q&A provide tangible illustrations to help manufacturers further understand FDA’s point of view.   

Consistent compliance

So, what should manufacturers consider as they look to develop “FDA-required labeling” consistent communications? In addition to the three factors already described, presentation of information is extremely important. Presentation (e.g. express and implied claims, overall impression of the net communication) must be truthful and accurate. To avoid a false or misleading presentation of communication, FDA recommends the following:

• Accurately represent the study

• Clearly disclose material aspects and limitations of the study – make this information stand out

• Disclose unfavorable or inconsistent findings

• Include data or information from the FDA-required labeling when the communication presents data or information not in the FDA-required labeling

While these recommendations are not exclusive, FDA does reinforce the notion that manufacturers have “qualified medical, legal and regulatory personnel carefully review the communication to ensure it is not false or misleading.”

To summarize, in its recently issued Q&A, FDA has given some insight into how manufacturers can share information that is not in the FDA-required labeling. Based on the recommendations and factors FDA will consider, there is a marginal opportunity for manufacturers to communicate information that it perhaps was unsure it could share in the past. For example, manufacturers may now consider communicating information like:

• Additional data from trials that replicate a registration trial (provided consistency of trial design to that used in support of the underlying label)

• Properly contextualized sub-group analysis of registration trial data

• Secondary endpoints from registration trials

• Quality of Life outcome assessments resulting from post-hoc analysis of the original registration trial

Provided these communications are appropriately contextualized, presented truthfully and the information is consistent with that in the approved label, manufacturers may now want to consider their ability to share this type of data. However, while the recently issued Q&A’s do present some opportunities, fundamental principles do not change. Consistent with the product label; truthful and not misleading. These are still the standards the FDA holds manufacturers accountable to in medical product promotional communications. 

Ruth Trzcienski is Compliance Director for Advertising, Public Relations and Medical Communication brands of inVentiv Health.